The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Evidence for a Mitochondrial Regulatory Pathway Defined by Peroxisome Proliferator–Activated Receptor-γ Coactivator-1α, Estrogen-Related Receptor-α, and Mitofusin 2
Abstract
Mitofusin 2 (Mfn2) is a mitochondrial membrane protein that participates in mitochondrial fusion and regulates mitochondrial metabolism in mammalian cells. Here, we show that Mfn2 gene expression is induced in skeletal muscle and brown adipose tissue by conditions associated with enhanced energy expenditure, such as cold exposure or β3-adrenergic agonist treatment. In keeping with the role of peroxisome proliferator–activated receptor-γ coactivator (PGC)-1α on energy expenditure, we demonstrate a stimulatory effect of PGC-1α on Mfn2 mRNA and protein expression in muscle cells. PGC-1α also stimulated the activity of the Mfn2 promoter, which required the integrity of estrogen-related receptor-α (ERRα)-binding elements located at −413/−398. ERRα also activated the transcriptional activity of the Mfn2 promoter, and the effects were synergic with those of PGC-1α. Mfn2 loss of function reduced the stimulatory effect of PGC-1α on mitochondrial membrane potential. Exposure to cold substantially increased Mfn2 gene expression in skeletal muscle from heterozygous Mfn2 knock-out mice, which occurred in the presence of higher levels of PGC-1α mRNA compared with control mice. Our results indicate the existence of a regulatory pathway involving PGC-1α, ERRα, and Mfn2. Alterations in this regulatory pathway may participate in the pathophysiology of insulin-resistant conditions and type 2 diabetes.
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“conditions that increase energy expenditure such as cold exposure, chronic exercise or nutraceuticals as resveratrol are associated with higher Mfn2 expression in skeletal muscle and brown adipose tissue in mice and humans (Cartoni et al., 2005; Dolinsky et al., 2013; Soriano et al., 2006).”
From Mitochondrial Activity and Dynamics Changes Regarding Metabolism in Ageing and Obesity (2017) · cites this paper as Soriano et al., 2006
In the citing paper
“Similar to many mitochondrial genes, Mfn2 expression is controlled by PGC-1α (Soriano et al, 2006), suggesting that decreased PGC-1α activity explains the defects in Mfn2 observed in obese and T2DM individuals.”
From Mitochondrial response to nutrient availability and its role in metabolic disease (2014) · cites this paper as Soriano et al, 2006
In the citing paper
“PGC-1α and its downstream target gene product, estrogen-related receptor-α (ERRα), stimulate the expression of Mfn2 (Cartoni et al., 2005; Soriano et al., 2006).”
From New insights into the role of mitochondria in aging: mitochondrial dynamics and more (2010) · cites this paper as Soriano et al., 2006
In the citing paper
“PGC-1 family members interact with the family of estrogen-related nuclear receptors, or ERRs, to transactivate transcription of oxidative genes (275) and mitofusins (276).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [276]
Citations
Cites
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A Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864
Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
Rodgers, J. T., Lerin, C., Haas, W., Gygi, S. P., Spiegelman, B. M., & Puigserver, P. (2005) · Nature · doi:10.1038/nature03354 · Cited by 3,160
Chen, H., Detmer, S. A., Ewald, A. J., Griffin, E. E., Fraser, S. E., & Chan, D. C. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211046 · Cited by 2,601
Self-citationTranscriptional co-activator PGC-1α drives the formation of slow-twitch muscle fibres
Lin, J., Wu, H., Tarr, P. T., Zhang, C.-Y., Wu, Z., Boss, O., Michael, L. F., Puigserver, P., Isotani, E., Olson, E. N., et al. (2002) · Nature · doi:10.1038/nature00904 · Cited by 2,546
Puigserver, P., & Spiegelman, B. M. (2003) · Endocrine Reviews · doi:10.1210/er.2002-0012 · Cited by 2,076
Patti, M. E., Butte, A. J., Crunkhorn, S., Cusi, K., Berria, R., Kashyap, S., Miyazaki, Y., Kohane, I., Costello, M., Saccone, R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1032913100 · Cited by 1,952
Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
Yoon, J. C., Puigserver, P., Chen, G., Donovan, J., Wu, Z., Rhee, J., Adelmant, G., Stafford, J., Kahn, C. R., Granner, D. K., et al. (2001) · Nature · doi:10.1038/35093050 · Cited by 1,821
Insulin-regulated hepatic gluconeogenesis through FOXO1–PGC-1α interaction
Puigserver, P., Rhee, J., Donovan, J., Walkey, C. J., Yoon, J. C., Oriente, F., Kitamura, Y., Altomonte, J., Dong, H., Accili, D., et al. (2003) · Nature · doi:10.1038/nature01667 · Cited by 1,487
CREB regulates hepatic gluconeogenesis through the coactivator PGC-1
Herzig, S., Long, F., Jhala, U. S., Hedrick, S., Quinn, R., Bauer, A., Rudolph, D., Schutz, G., Yoon, C., Puigserver, P., et al. (2001) · Nature · doi:10.1038/35093131 · Cited by 1,440
Cited by
Sorted by citations
Mitochondrial Dynamics in the Regulation of Nutrient Utilization and Energy Expenditure
Liesa, M., & Shirihai, O. S. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.002 · Cited by 1,341
“…of increased energy demand (i.e., exercise and cold exposure) and downregulated in type-2-diabetic patients (nutrient excess), involving the transcriptional coactivators PGC-1a and PGC-1b (Cartoni et al., 2005; Liesa et al., 2008; Soriano et al., 2006; Mootha et al., 2003; Patti et al., 2003).”
BackgroundSelf-citationMitochondrial Dynamics in Mammalian Health and Disease
Liesa, M., Palacín, M., & Zorzano, A. (2009) · Physiological Reviews · doi:10.1152/physrev.00030.2008 · Cited by 953
Self-citationTranscriptional control of mitochondrial biogenesis: the central role of PGC-1
Ventura-Clapier, R., Garnier, A., & Veksler, V. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn098 · Cited by 932
The Molecular Bases of Training Adaptation
Coffey, V. G., & Hawley, J. A. (2007) · Sports Medicine · doi:10.2165/00007256-200737090-00001 · Cited by 756
Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease
Misrani, A., Tabassum, S., & Yang, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.617588 · Cited by 654
Metadata
- Authors
- Soriano, F. X., Liesa, M., Bach, D., Chan, D. C., Palacín, M., & Zorzano, A.
- Affiliations
- Institute for Research in Biomedicine (ES)
- California Institute of Technology (US)
- Institute for Research in Biomedicine (IRB), Scientific Park of Barcelona, and Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2006-06-01
- Volume
- 55
- Issue
- 6
- Pages
- 1783-1791
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2109879006
- Semantic Scholar
- 17041cc2388633b2d920ee981de5eb2d025199be
- Cited by
- 343
- References
- 39
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 13 · 2023: 12 · 2022: 20 · 2021: 13 · 2020: 24 · 2019: 18 · 2018: 25 · 2017: 20 · 2016: 24 · 2015: 19 · 2014: 19 · 2013: 21 · 2012: 27
- FWCI
- 7.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- Johns Hopkins University
- Generalitat de Catalunya
- Instituto Danone
- Instituto de Salud Carlos III
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- mitofusin 2, PGC-1α, estrogen-related receptor alpha, mitochondrial fusion, mitochondrial metabolism, energy expenditure, cold exposure, beta3-adrenergic agonists, skeletal muscle, brown adipose tissue, transcriptional regulation, mitochondrial membrane potential, insulin resistance, type 2 diabetes
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Adipose Tissue, Brown, Cells, Cultured, Cold Temperature, Dioxoles, Heat-Shock Proteins, HeLa Cells, Humans, Male, Membrane Proteins, Mitochondria, Muscle, Protein Binding, RNA, Messenger, Transcription Factors, Transfection, Blotting, Western, Signal Transduction, Gene Expression, Rats, Wistar, Muscle, Skeletal, GTP Phosphohydrolases, Mitochondrial Proteins, Electrophoretic Mobility Shift Assay, Chromatin Immunoprecipitation, Estrogen Receptor alpha, Mice, Rats
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